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Trial record 17 of 185 for:    "Mitochondrial Diseases" OR "mitochondrial neurogastrointestinal encephalopathy disease"

Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease (MITO-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02023866
Recruitment Status : Completed
First Posted : December 30, 2013
Results First Posted : November 13, 2017
Last Update Posted : November 13, 2017
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Inherited Mitochondrial Disease, Including Leigh Syndrome
Intervention Drug: Cysteamine Bitartrate
Enrollment 36
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Period Title: Overall Study
Started 36
Completed 30
Not Completed 6
Reason Not Completed
Non-compliance             2
Adverse Event             3
Withdrawal by Subject             1
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Baseline Participants 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants
9.3  (4.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
Female
17
  47.2%
Male
19
  52.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
Hispanic or Latino
5
  13.9%
Not Hispanic or Latino
31
  86.1%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
American Indian or Alaska Native
3
   8.3%
Asian
0
   0.0%
Black of African American
0
   0.0%
Native Hawaiian or other Pacific Islander
0
   0.0%
White
28
  77.8%
Other
2
   5.6%
Multiple
3
   8.3%
Mitochondrial Disease Subtype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants
Leigh Syndrome
9
  25.0%
POLG-related disorders
7
  19.4%
MELAS
6
  16.7%
MERFF
4
  11.1%
Others
4
  11.1%
LHON
3
   8.3%
NUBPL Related Encephalopathy
2
   5.6%
Kearns-Sayre syndrome
1
   2.8%
[1]
Measure Description: LHON = leber hereditary optic neuropathy; MELAS = mitochondrial encephalomyopathy, lactic acidosis, and strokelike syndrome MERFF = myoclonic epilepsy and ragged-red fibers; NUBPL = Nucleotide Binding Protein-Like; POLG = Polymerase (DNA Directed), Gamma.
1.Primary Outcome
Title Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
Hide Description

The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains:

I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21; II -System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30.

III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28; and IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life.

Time Frame Baseline through Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Completers Analysis Set included all participants who received at least one dose of study drug (RP103) with at least one post-baseline NPMDS assessment and an evaluable Week 24 NPMDS assessment within the protocol specified window.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
Section I -0.3  (0.7)
Section II 0.1  (1.1)
Section III -0.6  (1.2)
Section IV 0.0  (4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cysteamine Bitartrate Delayed-release
Comments Section I - Current Function Null hypothesis = change from baseline is 0.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1875
Comments [Not Specified]
Method Wilcoxon Signed Rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cysteamine Bitartrate Delayed-release
Comments Section II - System Specific Involvement Null hypothesis = change from baseline is 0.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Wilcoxin Signed Rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cysteamine Bitartrate Delayed-release
Comments Section III - Current Clinical Assessment Null hypothesis = change from baseline is 0.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0781
Comments [Not Specified]
Method Wilcoxin Signed Rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cysteamine Bitartrate Delayed-release
Comments Section IV - Quality of Life Null hypothesis = change from baseline is 0.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2941
Comments [Not Specified]
Method t-test, 2 sided
Comments One-sample t-test
2.Secondary Outcome
Title Change From Baseline in Glutathione
Hide Description [Not Specified]
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The pharmacodynamic (PD) analysis set included all participants who received at least one dose of study drug and had at least one post-baseline PD assessment. Participants with available data at each time point are included in the analysis.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: µmol/L
Week 4 Number Analyzed 20 participants
16.8  (277.1)
Week 8 Number Analyzed 21 participants
141.5  (275.5)
Week 12 Number Analyzed 23 participants
10.2  (419.4)
Week 16 Number Analyzed 19 participants
88.7  (343.9)
Week 20 Number Analyzed 17 participants
51.4  (207.8)
Week 24 Number Analyzed 18 participants
122.4  (244.8)
3.Secondary Outcome
Title Change From Baseline in Glutathione Disulfide
Hide Description [Not Specified]
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD analysis set participants with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: µmol/L
Week 4 Number Analyzed 20 participants
29.4  (96.8)
Week 8 Number Analyzed 21 participants
-9.8  (43.9)
Week 12 Number Analyzed 23 participants
18.8  (105.3)
Week 16 Number Analyzed 19 participants
-11.2  (46.2)
Week 20 Number Analyzed 17 participants
0.8  (7.1)
Week 24 Number Analyzed 18 participants
-11.5  (47.6)
4.Secondary Outcome
Title Change From Baseline in Lactic Acid
Hide Description [Not Specified]
Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD analysis set participants with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: mmol/L
Week 4 Number Analyzed 28 participants
0.2  (1.0)
Week 8 Number Analyzed 25 participants
0.4  (1.6)
Week 12 Number Analyzed 27 participants
0.3  (2.4)
Week 16 Number Analyzed 26 participants
0.1  (1.2)
Week 20 Number Analyzed 24 participants
0.1  (1.1)
Week 24 Number Analyzed 27 participants
0.0  (1.2)
5.Secondary Outcome
Title Change From Baseline in 6 Minute Walk Test
Hide Description

The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: Myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.

Myopathy was assessed using the 6 minute walk test, which measures the distance walked in a 6 minute walk test.

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline 6 minute walk test assessment and for whom myopathy was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: meters
Week 4 Number Analyzed 13 participants
-23.5  (86.3)
Week 8 Number Analyzed 11 participants
-36.2  (73.3)
Week 12 Number Analyzed 10 participants
-14.5  (71.5)
Week 16 Number Analyzed 10 participants
-21.3  (90.6)
Week 20 Number Analyzed 9 participants
21.3  (61.9)
Week 24 Number Analyzed 9 participants
-18.9  (123.9)
6.Secondary Outcome
Title Change From Baseline in Jamar Dynamometer Hand Strength
Hide Description

The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.

Myopathy was assessed using standard grip strength evaluation, which measures hand strength in both hands using a Jamar dynamometer.

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline Jamar hand strength assessment and for whom myopathy was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: kg
Week 4 - Left hand Number Analyzed 9 participants
1.3  (2.4)
Week 8 - Left hand Number Analyzed 8 participants
1.1  (2.3)
Week 12 - Left hand Number Analyzed 7 participants
1.3  (2.6)
Week 16 - Left hand Number Analyzed 7 participants
0.0  (3.3)
Week 20 - Left hand Number Analyzed 7 participants
0.7  (3.1)
Week 24 - Left hand Number Analyzed 6 participants
1.3  (2.2)
Week 4 - Right hand Number Analyzed 9 participants
0.5  (3.0)
Week 8 - Right hand Number Analyzed 8 participants
1.6  (2.1)
Week 12 - Right hand Number Analyzed 7 participants
1.6  (2.6)
Week 16 - Right hand Number Analyzed 7 participants
0.7  (2.9)
Week 20 - Right hand Number Analyzed 7 participants
0.9  (2.4)
Week 24 - Right hand Number Analyzed 6 participants
1.2  (2.1)
7.Secondary Outcome
Title Change From Baseline in Barry-Albright Dystonia Scale Total Score
Hide Description

The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.

Dystonia symptoms were assessed using the Barry-Albright Dystonia Scale for Dystonia. Participants were assessed for dystonia in each of the following regions: eyes, mouth, neck, trunk, and each upper and lower extremity (8 body regions) on a scale from 0 (absent) to 4 (severe symptoms). The individual scores were summed to calculate the total score which ranges from 0 (dystonia absent) to 32 (severe dystonia).

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline dystonia assessment and for whom dystonia was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 Number Analyzed 4 participants
1.3  (1.0)
Week 8 Number Analyzed 3 participants
0.7  (0.6)
Week 12 Number Analyzed 3 participants
0.3  (3.1)
Week 16 Number Analyzed 3 participants
0.3  (3.1)
Week 20 Number Analyzed 3 participants
-0.7  (4.7)
Week 24 Number Analyzed 3 participants
0.7  (3.5)
8.Secondary Outcome
Title Change From Baseline in Friedreich Ataxia Rating Scale
Hide Description

The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.

Ataxia was assessed using the Friedreich Ataxia Rating Scale (FARS). FARS comprises a functional ataxia staging score of overall mobility (score 0 to 6), an assessment of the activities of daily living (ADL) (score 0 to 36) and a neurological assessment (score from 0 to 117) which is composed of bulbar (score 0-11), upper limb (score 0- 36) and lower limb (score 0-16), peripheral nerve (score 0-26) and upright stability/gait (score 0-28). The scores were summed to calculate the total score which ranges from 0 to 159. A higher score indicates a greater level of disability.

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline ataxia assessment and for whom ataxia was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 16.9  (27.2)
Week 8 13.9  (25.6)
Week 12 15.9  (23.1)
Week 16 19.4  (23.0)
Week 20 16.5  (21.5)
Week 24 20.5  (18.5)
9.Secondary Outcome
Title Change From Baseline in Gross Motor Function
Hide Description

The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit.

Retarded motor development was assessed using the Gross Motor Function Measure (GMFM)-88 which consists of 88 items scored on a scale of 0 to 3:

0: Does not initiate the task;

  1. Initiates the task (completes < 10%);
  2. Partially completes the task (10 to 99%);
  3. Completes the task (100%).

The 88 items are grouped into five dimensions: 1) lying and rolling, 2) sitting, 3) crawling and kneeling, 4) standing, and 5) walking, running and jumping. Scores are expressed as a percentage of the maximum score for that dimension. The total score is the average of the 5 the percentage scores where higher scores indicate better performance.

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline gross motor function assessment and for whom retarded motor development was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 0.4  (4.3)
Week 8 0.9  (7.9)
Week 12 0.5  (3.6)
Week 16 4.4  (5.6)
Week 20 4.0  (8.2)
Week 24 2.2  (8.2)
10.Secondary Outcome
Title Change From Baseline in Modified Lansky Play Performance Scale
Hide Description

The investigator selected the 2 most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms were assessed at each subsequent study visit.

Reduced activities of daily living was assessed using the modified Lansky Play Performance Scale, completed by parents based on their child’s activity in the past week, where 100=fully active; 90=minor restrictions in strenuous physical activity; 80=active, gets tired more quickly; 70=greater restriction of play, less time spent in play activity; 60=up and around, active play minimal; quieter activities; 50=lying around much of the day; no active playing, all quiet play and activities; 40=mainly in bed; quiet activities; 30=bedbound; needs assistance even for quiet play; 20=sleeps often; play limited to very passive activities; 10=doesn't play or get out of bed; 5=unresponsive 0=dead

Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug (RP103) and had at least one post-baseline Lansky play performance scale assessment and for whom reduced activities of daily living was prespecified as a preeminent symptom and with available data at each time point.
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 4 Number Analyzed 5 participants
-2.0  (4.5)
Week 8 Number Analyzed 5 participants
-6.0  (8.9)
Week 12 Number Analyzed 5 participants
-2.0  (4.5)
Week 16 Number Analyzed 5 participants
2.0  (11.0)
Week 20 Number Analyzed 5 participants
-4.0  (11.4)
Week 24 Number Analyzed 5 participants
-6.0  (8.9)
Time Frame 24 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cysteamine Bitartrate Delayed-release
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
All-Cause Mortality
Cysteamine Bitartrate Delayed-release
Affected / at Risk (%)
Total   1/36 (2.78%) 
Show Serious Adverse Events Hide Serious Adverse Events
Cysteamine Bitartrate Delayed-release
Affected / at Risk (%)
Total   11/36 (30.56%) 
Cardiac disorders   
Atrioventricular block complete  1  1/36 (2.78%) 
Atrioventricular block second degree  1  1/36 (2.78%) 
Cardiomyopathy  1  1/36 (2.78%) 
Gastrointestinal disorders   
Vomiting  1  3/36 (8.33%) 
Constipation  1  1/36 (2.78%) 
General disorders   
Pyrexia  1  1/36 (2.78%) 
Infections and infestations   
Adenovirus infection  1  1/36 (2.78%) 
Ear infection  1  1/36 (2.78%) 
Urinary tract infection  1  1/36 (2.78%) 
Metabolism and nutrition disorders   
Dehydration  1  2/36 (5.56%) 
Hyperglycaemia  1  1/36 (2.78%) 
Nervous system disorders   
Convulsion  1  2/36 (5.56%) 
Lethargy  1  1/36 (2.78%) 
Status epilepticus  1  1/36 (2.78%) 
Psychiatric disorders   
Mental status changes  1  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory arrest  1  1/36 (2.78%) 
Surgical and medical procedures   
Cardiac pacemaker insertion  1  1/36 (2.78%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cysteamine Bitartrate Delayed-release
Affected / at Risk (%)
Total   35/36 (97.22%) 
Cardiac disorders   
Sinus tachycardia  1  1/36 (2.78%) 
Ear and labyrinth disorders   
Motion sickness  1  1/36 (2.78%) 
Eye disorders   
Eye movement disorder  1  1/36 (2.78%) 
Eye pain  1  1/36 (2.78%) 
Eyelid oedema  1  1/36 (2.78%) 
Eyelid ptosis  1  2/36 (5.56%) 
Mydriasis  1  1/36 (2.78%) 
Ocular hyperaemia  1  1/36 (2.78%) 
Gastrointestinal disorders   
Abdominal discomfort  1  1/36 (2.78%) 
Abdominal distension  1  1/36 (2.78%) 
Abdominal pain  1  7/36 (19.44%) 
Abdominal pain upper  1  4/36 (11.11%) 
Breath odour  1  12/36 (33.33%) 
Constipation  1  4/36 (11.11%) 
Diarrhoea  1  15/36 (41.67%) 
Eructation  1  1/36 (2.78%) 
Faecal incontinence  1  1/36 (2.78%) 
Flatulence  1  1/36 (2.78%) 
Gastroesophageal reflux disease  1  1/36 (2.78%) 
Haematemesis  1  1/36 (2.78%) 
Nausea  1  12/36 (33.33%) 
Retching  1  1/36 (2.78%) 
Salivary hypersecretion  1  1/36 (2.78%) 
Vomiting  1  21/36 (58.33%) 
General disorders   
Asthenia  1  1/36 (2.78%) 
Chest pain  1  2/36 (5.56%) 
Fatigue  1  11/36 (30.56%) 
Gait disturbance  1  2/36 (5.56%) 
Malaise  1  1/36 (2.78%) 
Pyrexia  1  12/36 (33.33%) 
Infections and infestations   
Bursitis infective  1  1/36 (2.78%) 
Croup infectious  1  1/36 (2.78%) 
Gastroenteritis viral  1  1/36 (2.78%) 
Influenza  1  5/36 (13.89%) 
Nasopharyngitis  1  4/36 (11.11%) 
Oral herpes  1  1/36 (2.78%) 
Otitis media  1  1/36 (2.78%) 
Pharyngitis streptococcal  1  3/36 (8.33%) 
Rhinovirus infection  1  1/36 (2.78%) 
Tooth infection  1  1/36 (2.78%) 
Upper respiratory tract infection  1  2/36 (5.56%) 
Viral infection  1  1/36 (2.78%) 
Injury, poisoning and procedural complications   
Contusion  1  2/36 (5.56%) 
Foot fracture  1  1/36 (2.78%) 
Laceration  1  2/36 (5.56%) 
Radial head dislocation  1  1/36 (2.78%) 
Investigations   
Alanine aminotransferase increased  1  1/36 (2.78%) 
Amylase increased  1  1/36 (2.78%) 
Aspartate aminotransferase increased  1  1/36 (2.78%) 
Blood alkaline phosphatase increased  1  1/36 (2.78%) 
Blood bicarbonate decreased  1  1/36 (2.78%) 
Blood creatine phosphokinase increased  1  1/36 (2.78%) 
Blood creatinine increased  1  1/36 (2.78%) 
Blood glucose increased  1  1/36 (2.78%) 
Blood urea increased  1  1/36 (2.78%) 
Clostridium test positive  1  1/36 (2.78%) 
Ejection fraction decreased  1  1/36 (2.78%) 
Electrocardiogram abnormal  1  1/36 (2.78%) 
Gamma-glutamyltransferase increased  1  1/36 (2.78%) 
Respiratory rate decreased  1  1/36 (2.78%) 
Weight decreased  1  2/36 (5.56%) 
Metabolism and nutrition disorders   
Acidosis  1  1/36 (2.78%) 
Decreased appetite  1  14/36 (38.89%) 
Dehydration  1  1/36 (2.78%) 
Diabetes mellitus  1  1/36 (2.78%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/36 (2.78%) 
Muscle atrophy  1  1/36 (2.78%) 
Muscle spasms  1  1/36 (2.78%) 
Muscle tightness  1  2/36 (5.56%) 
Muscular weakness  1  1/36 (2.78%) 
Pain in extremity  1  2/36 (5.56%) 
Posture abnormal  1  1/36 (2.78%) 
Nervous system disorders   
Akathisia  1  1/36 (2.78%) 
Ataxia  1  1/36 (2.78%) 
Balance disorder  1  1/36 (2.78%) 
Convulsion  1  4/36 (11.11%) 
Disturbance in attention  1  1/36 (2.78%) 
Dizziness  1  1/36 (2.78%) 
Dysgeusia  1  1/36 (2.78%) 
Dystonia  1  3/36 (8.33%) 
Encephalopathy  1  1/36 (2.78%) 
Headache  1  7/36 (19.44%) 
Lethargy  1  8/36 (22.22%) 
Migraine  1  1/36 (2.78%) 
Parkinsonian rest tremor  1  1/36 (2.78%) 
Peroneal nerve palsy  1  1/36 (2.78%) 
Somnolence  1  2/36 (5.56%) 
Speech disorder  1  1/36 (2.78%) 
Tremor  1  3/36 (8.33%) 
Psychiatric disorders   
Abnormal behaviour  1  1/36 (2.78%) 
Agitation  1  2/36 (5.56%) 
Anxiety  1  1/36 (2.78%) 
Depression  1  1/36 (2.78%) 
Insomnia  1  1/36 (2.78%) 
Irritability  1  2/36 (5.56%) 
Mental status changes  1  1/36 (2.78%) 
Mood swings  1  2/36 (5.56%) 
Restlessness  1  1/36 (2.78%) 
Sleep disorder  1  1/36 (2.78%) 
Tic  1  1/36 (2.78%) 
Renal and urinary disorders   
Pollakiuria  1  2/36 (5.56%) 
Urinary retention  1  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders   
Bronchospasm  1  1/36 (2.78%) 
Cough  1  3/36 (8.33%) 
Dyspnoea  1  1/36 (2.78%) 
Epistaxis  1  1/36 (2.78%) 
Oropharyngeal pain  1  1/36 (2.78%) 
Rhinorrhoea  1  1/36 (2.78%) 
Rhonchi  1  1/36 (2.78%) 
Wheezing  1  1/36 (2.78%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/36 (2.78%) 
Eczema  1  1/36 (2.78%) 
Hair colour changes  1  6/36 (16.67%) 
Rash  1  1/36 (2.78%) 
Skin depigmentation  1  1/36 (2.78%) 
Skin disorder  1  1/36 (2.78%) 
Skin odour abnormal  1  7/36 (19.44%) 
Vascular disorders   
Pallor  1  1/36 (2.78%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors’ Intellectual Property rights .
Results Point of Contact
Name/Title: Evelyn Olson, Director
Organization: Horizon Pharma USA, Inc.
Phone: 224- 383-3000
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT02023866     History of Changes
Other Study ID Numbers: RP103-MITO-001
First Submitted: December 17, 2013
First Posted: December 30, 2013
Results First Submitted: October 13, 2017
Results First Posted: November 13, 2017
Last Update Posted: November 13, 2017